Neurofilament levels may help diagnose adult-onset SMA vs ALS

The amount of neurofilament proteins found in the cerebrospinal fluid, the liquid surrounding the brain and spinal cord, may help doctors better distinguish between adult-onset spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS), a study found.

The two conditions are marked by damage to motor neurons, the specialized nerve cells responsible for motor movement, and are sometimes difficult to distinguish via symptoms or diagnostic tests.

Now, these results show that neurofilament light chain (NfL) and neurofilament heavy chain (NfH) — whose levels are often used as markers of nerve damage — “might be useful biomarkers for differential diagnosis of adult SMA and ALS,” according to researchers.

Indeed, the team found significantly lower NfL levels in people with SMA compared with ALS patients.

The study, “Comparison of neurofilament light and heavy chain in spinal muscular atrophy and amyotrophic lateral sclerosis: A pilot study,” was published in the journal Brain and Behavior.

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Differences in neurofilament levels seen in SMA and ALS adults

In both SMA and ALS, the gradual loss of motor neurons results in progressive muscle weakness and wasting, leading to severe disability. SMA onset typically occurs during childhood or adolescence, which makes it “easy to identify,” the researchers wrote.

However, when the condition develops in adulthood, as happens for those with type 4 SMA, the mildest form of the disease, patients may be initially misdiagnosed with ALS.

“It is often difficult to distinguish adult SMA patients and ALS patients … by clinical symptoms or electromyography,” which is the use of nerve conduction studies, the researchers wrote.

With this in mind, a team of researchers in China launched a pilot study to seek potential biomarkers that could help distinguish between the two conditions. The end goal would be finding tests that could work when symptoms or diagnostic assessments are inconclusive.

Blood and CSF samples, collected at hospital admission from 10 adults with SMA, were examined. The patients had a mean age of 26.8, and had been admitted to the Peking Union Medical College Hospital, in Beijing, from October 2019 to April 2022.

The samples were compared with those from 10 ALS patients and 10 healthy people, who served as controls. The mean age of these individuals — 50 for the ALS patients and 46.4 for the controls — was significantly older than that of the SMA group members.

The investigators measured levels of the neuronal damage biomarkers, including NfL and phosphorylated NfH (pNfH), as well as markers of muscle damage, such as creatine kinase (CK) and creatinine.

The results showed that blood levels of NfL and pNfH were significantly elevated in ALS patients compared with the controls, but no differences were observed between SMA patients and controls.

However, a comparison between SMA and ALS patients found that CSF levels of both NfL and pNFH were significantly lower in the SMA group. There also were significant differences in blood creatinine levels, which were similarly lower in the SMA group.

This pilot study … found significantly lower CSF levels of NFL and pNFH in SMA patients than in ALS patients, indicating the potential diagnostic value of [neurofilament proteins].

Additional analyses showed that all three markers showed a significant value in differentiating the two conditions. For example, a cut-off value of 44.5 micromoles/L for blood creatinine could distinguish ALS from SMA with a 90% sensitivity or true-positive rate and a 90% specificity or true-negative rate.

A 0.395 nanograms/mL cut-off for CSF pNfH showed a 90% sensitivity and 80% specificity. However, CSF NfL had the best performance in distinguishing the two conditions, with a 1,275 picograms/mL cut-off showing 100% specificity and sensitivity.

Overall, “this pilot study … found significantly lower CSF levels of NFL and pNFH in SMA patients than in ALS patients, indicating the potential diagnostic value of [neurofilament proteins],” the team wrote.

Among the study’s limitations, as noted by researchers, were its small size and the differences in age between SMA and ALS patients, which may affect neurofilament levels.

“Further studies with larger sample sizes and matched controls” will now be needed to confirm the findings, the team noted.